Tuesday, July 5, 2011

Liposuction and Fat Regain

If body fat really is actively regulated by the body, rather than just being a passive result of voluntary food intake and exercise behaviors, then liposuction shouldn't be very effective at reducing total fat mass in the long run. People should return to their body fat "setpoint" rather than remaining at a lower fat mass.

Teri L. Hernandez and colleagues recently performed the first ever randomized liposuction study to answer this question (1). Participants were randomly selected to either receive liposuction, or not. They were all instructed not to make any lifestyle changes for the duration of the study, and body fatness was measured at 6 weeks, 6 months and one year by DXA.

At 6 weeks, the liposuction group was significantly leaner than the control group. At 6 months, the difference between the two groups had decreased. At one year, it had decreased further and the difference between the groups was no longer statistically significant. Furthermore, the liposuction group regained fat disproportionately in the abdominal area (belly), which is more dangerous than where it was before. The investigators stated:

We conclude that [body fat] is not only restored to baseline levels in nonobese women after small-volume liposuction, but is redistributed abdominally.

This is consistent with animal studies showing that when you surgically remove fat, total fat mass "catches up" to animals that had no fat removed (2). Fat mass is too important to be left up to chance. That's why the body regulates it, and that's why any satisfying resolution of obesity must address that regulatory mechanism.

114 comments:

Bodybuilders are now turning to a new class of drugs which target the dopamine system, instead of the usual testosterone, steroids and insulin shots of yesteryear. It seems drugs for Parkinson's such as Ergotamine and Pergolide, which are D2 agonists and D1 antagonists, have the side effect of causing rapid bodyfat loss and muscle gain. Subjects report that they have to eat upwards of 7000 kcals/day just to maintain their bodyfat levels, and if they eat any less, they get very ripped without losing muscle mass (and if they exercise, they gain profound amounts of lean mass very easily).

If this is true, there seems to be some kind of nutrient partitioning mechanism responsible or how much fat to lean ratio one has, and this mechanism seems to be intimately related to dopamine communication. This reveals not JUST a bodyfat regulator, but an overall body "design" program controlled by the brain, depending on its stimuli from the outside world (taste and availability of food, and maybe other things too).

So what do overall calories mean, given what you know about setpoints? If everything is so tightly controlled by the brain, I don't understand why eating more or less make a difference.

Not surprising, they eat the same amount as they did before the lipo so they regain the fat. No diet adjustment after fat loss, whether through calorie restriction or liposuction and you're most likely gonna gain it back.

Gastric bypass works by reducing nutrient volume entering the blood stream, which in turn reduces insulin surges. If your small intestine has been bypassed, you are limited in how much you can spike your insulin.

For an example of what happens to the human metabolism when there is an abnormal loss of adipocytes, examine someone with lipodystrophy. This is a disease where there is a death of fat cells. Meaning, there is no where for fatty acids and glucose to go.

These people develops severe metabolic disease, tons of visceral fat, fatty liver, triglycerides in the thousands, intractable diabetes, all while emaciating... they don't have fat cells. Their leptin levels are almost undetectable as well, for this reason (leptin is made first by basal fat cells, and second by insulin stimulating nutrient uptake in the fat cell - someone with nearly no fat cells will have no leptin).

Injecting leptin into these people reduces a lot of their metabolic disease (as metabolic syndrome/glucose intolerance is symptomatic of leptin insufficiency). However, they still remain diabetic due to an intrinsic lack of fat tissue.

When people look at a person fluffy with body fat we think "oh that fat ass has an excessive amount of fat - just suck it out with a catheter under anesthesia and they will be good as new" Um newp! That fat storage IS AN ADAPTATION to an inability to use glucose normally. The body grows new fat cells as a direct response to high insulin levels, which in turn is stimulated by high glucose levels. A fat person may never once test over 130 on a glucometer - but if your insulin is surging to mop up your glucose you will get hugely fat unless you are a genetic freak. Many fat people don't realize their problem is at root a glucose metabolism disorder. Why would they, their glucose is always normal. What they don't realize is their insulin is surging many times the normal level in response to the same food intake as a "normal thin" person and this is precisely why they are so fat.

So when you remove the fat tissue of a fat person - fat tissue the body grew ON PURPOSE to cope with glucose it cannot process normally - don't be surprised when they start to resemble someone with lipodystrophy. Hyperglycemia and visceral fat and higher triglycerides, i.e. hastening the onset of metabolic decompensation (which is what the fat tissue was protecting against in the first place).

To arrest and partially correct existent obesity, one must control the insulin level and this is first and foremost accomplished with carbohydrate restriction.

Fat cell removal surgery is very useful after successful control of insulin levels, i.e. in a dieted post obese person who is maintaining a healthful glucose balancing diet.

Speaking personally, as someone who has had numerous skin removal sugeries (SKIN has adipocytes attached) I did not develop an excess of visceral fat. This did not happen because my diet does not produce glucose surges.

My adipocytes were no longer needed, like a cocoon of a butterfly - the excessive fat tissue my body grew in my teen years is no longer necessary, my insulin is no longer surging that high as my diet is no longer assaulting my body with glucose it cannot process normally.

In my case, the adipocytes were not "just right", but more like scar tissue, a snake skin I malt, the remnants of a condition I no longer require. I will NEVER spike my insulin that high again as I know everything about how to control metabolic disorder and obesity.

However, pull a fat person off the street, they need every single fat cell they have to avoid hastening the onset of decompensation of metabolic state... sucking them out will only make them diabetic.

Removing visceral fat is the exception to this rule as it is inflammatory and actually CAUSES glucose intolerance.

White adipose PROTECTS against glucose intolerance by providing an insulin responsive depot for glucose and fatty acids (which may be why women are more resistant to metabolic disorders than men - female hormones help fat cells to grow, white fat tissue, women in general find it very easy to fatten)

Stephen-I'm interested in your response to the ItsTheWoo2 (and my post as well). Seems he/she is missing something-maybe the excess nutrition consumption part. Insulin spikes and over-fat, as far as I can tell, only seem to be correlated when there is excess calorie consumption. As far as I know, you can spike insulin all day long and, as long as you take in less than you expend, you will reduce fat as well (ex. the potato diet and the Twinkie diet). The common denominator here: calories. (this says nothing about the nature of food and what it does to your hunger of course)

@ItsTheWooo2: I'm not sure all carbs are equal - I am still eating fresh fruits and vegetables, as well as nuts and dried fruit. Granted, it's not a high volume and none of it is sweetened, but it's still carbs.

The idea is not that they gained because they ate a lot - in that case, the control group would have gained, too, and stayed ahead of the liposuction group. The idea is that the bodies of these guys had a certain target weight and moved toward that weight regardless of where they started. (And that liposuction didn't change that target weight.)

I never said insulin alone makes you fat. Insulin the context of being a free range human that can eat as much as it wants (i.e. respond to hunger normally) is what makes you fat.

If you spike someones insulin in a lab over and over but prevenet them from eating in response to the fat storage, all that will happen is this person or animal will frequently become hyp9oglycemic, and probably feel extremely hungry - but their body mass won't increase appreciably. You can't fuel a fire without kindling.

They won't look and feel like a normal person - they will have waste dmuscle tissue, disproprotionate fat tissue, be lethargic frequently hungry not to mention hypoglycemic.

However this has no relevance to REAL PEOPLE IN THE REAL WORLD. Real people eat when they are starvingly hungry - just like you do. If a real person has a flood of insulin when they eat pasta, rice or potatoes, they are going to eat a ton of calories and store it all as fat.

Yes, the excess calorie consumption is the key. Insulin spikes do not increase food intake unless they cause hypoglycemia. In fact, insulin is kind of like leptin's kid brother: it acts in the brain to constrain fat mass.

Also, insulin is co-secreted with amylin, which also constrains fat mass by increasing satiation and possibly leptin sensitivity.

All this postprandial insulin spikes = fat gain stuff is nonsense as far as I can tell. I still haven't seen a shred of convincing evidence to support it, and in fact, the evidence I've seen mostly supports the opposite hypothesis, that insulin spikes oppose fat gain. The idea that postprandial insulin causes fat gain is contradicted by the most basic empirical facts in both human and animal studies. As I said before, I don't know a single person who studies metabolism/endocrinology professionally who takes that idea seriously-- it is confined to the popular press and internet blogs/forums.

@ItsTheWoo2-what you are saying is that insulin in response to food intake makes you overeat, correct? Due to a hypoglycemic effect? I've heard that true hypoglycemia is rare, seen mostly in people who inject too much insulin (maybe Stephen can clear this up?) I did read in a Jenny Ruhl book that if your blood sugar is normally high (I guess due to IR or hepatic IR) and it drops from there, you will FEEL hypoglycemic, although blood sugar is normal (it was something like that). This could possibly lead you to eat to reduce hypoglycemic symptoms, although I doubt it automatically leads to big overeating. Either way I don't think insulin has much of a connection to causing insulin resistance, and likely provides a satiety effect.

So the argument is that insulin indirectly makes you fat by making you massively hungry and causing you to overeat. I just don't think that is correct, but I'll keep my mind open.

My personal experience is that I don't gain fat, whether eating high or low carb, even when I have occasional binges, unless I continuously overeat. So although I may be storing those calories as fat (high insulin temporarily reduces FFA release (not increased carbs to fat)if intake is low enough, this doesn't matter much. High dietary fat can go right to the fat cells, but wont stay there long if intake is low enough), It doesn't stay there long unless I'm eating more than I need. Again, the common denominator here is calories, not insulin.

"In fact, insulin is kind of like leptin's kid brother: it acts in the brain to constrain fat mass."

Would you say that this provides good reason to at least include some starch in our daily diet, maybe even at every meal (assuming no pathological blood sugar regulation problem), especially for those who want to lose weight?

Also, while I generally like a paleo type diet, it has become apparent to me that it's effect has everything to do with its potential in reducing food intake ad libitum, not in controlling insulin. Since food intake motivation is so multifactorial-this obviously doesn't work for everyone as a careful look through the paleo blogs clearly shows.

you posts on food reward are extremely interesting and motivated me to also start reading The End of Overeating by David Kessler, MD. I've come to the conclusion that in this day and age, with food advertising and availability, a weight loss/healthy diet really does take some effort and will power (reduced gluttony and sloth, if you will) and those who say otherwise aren't doing anyone any favors.

As always, I keep my mind open to new suggestions and ideas (although extraordinary claims requires extraordinary proof).

I didn't say they ate "a lot", I said they're diet wasn't adjusted to take in account their lower calorie needs thus they over ate. Again, their intake exceeded their new body weight calorie requirements so they as expected, re-accumulated fat mass.

Why would the control group gain anything if they're eating as they usually do? There's no deliberate overfeeding.

"All this postprandial insulin spikes = fat gain stuff is nonsense as far as I can tell. I still haven't seen a shred of convincing evidence to support it, and in fact, the evidence I've seen mostly supports the opposite hypothesis, that insulin spikes oppose fat gain. The idea that postprandial insulin causes fat gain is contradicted by the most basic empirical facts in both human and animal studies. As I said before, I don't know a single person who studies metabolism/endocrinology professionally who takes that idea seriously-- it is confined to the popular press and internet blogs/forums. "

Annnnd this is why you will never help anyone lose any weight, meanwhile I know how to cure obesity.

Besides even if "true hypoglycemia" is rare, it is TOTALLY IRRELEVANT as relative hypoglycemia produces the same hunger and adrenal hyperactivity as absolute hypoglycemia. If your sugar goes from 140 to 80 in 30 minutes, you are going to be shaking, hysterical, and ravenous.It's the sudden drop in nutrients in the blood stream that triggers your brain and body to go EAT EAT EAT.

Most fat people have abnormal insulin surges, which is why they eat more on a carb diet and eat much less on a ketogenic low carb one.

"Annnnd this is why you will never help anyone lose any weight, meanwhile I know how to cure obesity."

How's the Cool-Aid?

"Most fat people have abnormal insulin surges, which is why they eat more on a carb diet and eat much less on a ketogenic low carb one."

An exaggeration. Some fat people secrete too much insulin and low carb reduces hunger and works well for them. Others have a normal insulin response and wont respond like this. Everyone still needs to eat less than they expend to lose.

Carbohydrates (lots of them) have been in our diet for a very very long time, yet rampant obesity is recent. Do you really think carbohydrate is the problem? That it causes abnormal insulin secretion, overeating and fatness (a ketogenic diet as cure would assume carbs are the problem)? What's different now vs. before the obesity epidemic? Stephen's food reward posts make more sense to me.

Obesity is a phenotype, not a disease and its cause is multi-factorial. People eat and overeat for various reasons, hunger being one. If you think you can cure all obesity based on insulin and cortisol, well, good luck.

The more I read about the brain, the more I'm realizing that fat gain or loss might not be about either calories OR insulin. There are just too many people that can eat as much and whatever they want without getting fat. (That's not to say they are healthy though, which is another matter.)

This is certainly a top-down process, where the brain is boss. Even if a fit person "overeats" on calories, her body will burn off those calories and/or she'll get the urge to get off her butt and do physical activity. So how can calories matter? Or insulin?

Hi Kris, neither insulin nor calories explains why both slim people and obese people stay within 1-2 lbs of their usual weight for decades, with rock-stable BMI and bodyfat percentages.

Atributing the cause to either calories or insulin implies that for their whole lives, rain or shine, in sickness or in health, as they slowly age, they have been eating and/or burning the EXACT SAME AMOUNT of calories every day(in the calorie case) or that their insulin has moved in EXACTLY THE SAME PATTERN every day.

Just subscribing, really interested in this type of stuff as the calorie-in/calorie-out perspective definitely works in the short-term but doesn't seem to be a viable long-term solution for a healthy and lean body.

Also, extending on gunther gatherer's first comment, do any foods mimic the effects on D2 and D1 as seen by the drugs?

The current/traditional thinking in many groups is that one should eat more starchy carbs only as they get leaner due to an improved insulin resistance profile as you get leaner. Do you know of any research to back this up? This approach is usually combined with eating "clean" foods at a slight calorie deficit in pursuit of leaning out.

"The more I read about the brain, the more I'm realizing that fat gain or loss might not be about either calories OR insulin. There are just too many people that can eat as much and whatever they want without getting fat. (That's not to say they are healthy though, which is another matter.) "

money quote, i have been saying this for years. it is ALL about the brain- but everyone's brain is different, wires differently and translates chemicals differently. diet really only plays a small SMALL role in all this

Female 37 years old, 5'4" used to weigh a flabby 165 pounds without exercise no matter what I ate. Discovered low carb WOE and lost twenty pounds over 2 years, maintained a flabby 145 for two years with little more than running 10 miles per week. Decided to have abdominoplasty and liposuction around my waist. The surgeon asked me to lose ten pounds so that he would have extra skin to work with for the tummy tuck. I lost down to 134 on the day of the surgery two years ago via starvation (0-500 calories per day for a month). One year post-surgery gained back to my setpoint at 145 pounds. All of the weight regain is in my hips, butt and thighs, however I still have the tight stomach and small waist. Everyone asks me if it was worth it and I am not sure. I really love the abs, but I went into surgery with a size 10 waist and size 6 hips. Now I have a size 6 waist and a size 8 hips, so it was really just a rearranging of fat. Two years post-surgery I did not have enough hours in the day to run enough miles to stop the lower-body regain and I have had to really increase weight training to see any results. I think liposuction is temporary and most if not all of the fat will come back in another area even in the absence of over eating.

Certainly it's more complicated than calories in calories out, but that is still baseline, basic and true. Why people eat to excess is another story and the possibilities are huge.

It's not all about hunger, and hunger may even be in the minority. Calories don't explain why people can stay weight stable with varying levels of intake, but what the body does with those calories and how it regulates can explain things. For example, do you have increased spontaneous expenditure after eating more? Does one spontaneously reduce intake after eating a lot (reduces hunger)? This would indicate a healthy regulatory mechanism and I think leptin fits in here.

But what of those who cannot say no to donuts brought in daily at work, even if they really aren't that hungry? Or those who must have a Starbucks coffee milkshake every morning as part of their daily routine, even if they aren't hungry? Has anyone ever eaten desert even after being full from dinner? Anyway, why people do what they do is so variable, it's hard to pidgin-hole everyone as fat due to hormones.

Avoiding carbohydrate can facilitate weight loss. I believe that's mostly because of its effect on food reward, although at extremely low levels it causes ketosis, which may further facilitate fat loss. I'm not against low-carb diets for fat loss, but I think for most people it's not going to be the best lifetime maintenance diet for health. I think if there is an optimal diet for most people, it's one that includes a liberal amount of starch.

I do think eating healthy and losing weight requires some willpower, but not the same kind that most people talk about. It's about choosing the right foods more than deliberately restricting how much you eat. I believe the former is much easier than the latter in the long term, and probably healthier as well.

Hi Unknown,

I think it's probably part of the truth. I do believe that lipoproteins are causally related to vascular disease, and the cholesterol measurements probably reflect that to some degree. We don't know how much atherosclerosis the Kitavans have because there haven't been autopsies to my knowledge (although other traditionally-living Melanesians tend not to have much athero). But the path to heart attacks is complex, and involves more than just atherosclerosis. So yes, I do think lipids may partially just be a marker of diet, which acts in many ways to determine heart attack risk. But I don't know the degree to which that is true.

Hi bentleyj74,

I don't expect every person to react well on a high-starch diet. There are individual differences, due to heritable factors and previous metabolic damage. I certainly wouldn't advise someone to stick with it if they gave it a solid chance and it really makes them feel bad. But high starch diets can be healthy for most people-- there is a large body of literature supporting that conclusion. The majority of the world eats a high-starch diet, and has less obesity/metabolic disease than the US.

Hi Kris,

What insulin does is coordinate the switch from primarily burning fatty acids to primarily burning carbohydrate. Insulin turns on glucose burning when there is glucose around, because the body can't store much glucose-- so it gets metabolic priority. But if you look at 24 hr energy expenditure, it doesn't change significantly whether the calories are coming from fat or carbohydrate-- the same number of calories are being burned in both cases. If you eat fat, the body burns the fat you ate; if you eat carb, the body burns the carb you ate. What that means is that energy (fat) accumulation in the body is controlled by calorie intake, not macronutrients or insulin signaling.

If insulin spikes caused fat accumulation independently of calories, you would not see weight loss in low-fat diet trials, and you would not see so many lean high-carb cultures.

Stephen, "All this postprandial insulin spikes = fat gain stuff is nonsense as far as I can tell. I still haven't seen a shred of convincing evidence to support it, and in fact, the evidence I've seen mostly supports the opposite hypothesis, that insulin spikes oppose fat gain. The idea that postprandial insulin causes fat gain is contradicted by the most basic empirical facts in both human and animal studies. As I said before, I don't know a single person who studies metabolism/endocrinology professionally who takes that idea seriously-- it is confined to the popular press and internet blogs/forums." Perhaps you haven't read Gary Taubes' "Good Calories, Bad Calories", in which he provides a mountain of both epidemiological and biochemical evidence. Thomas,"Carbohydrates (lots of them) have been in our diet for a very very long time, yet rampant obesity is recent. Do you really think carbohydrate is the problem? That it causes abnormal insulin secretion, overeating and fatness (a ketogenic diet as cure would assume carbs are the problem)? What's different now vs. before the obesity epidemic?" What's different now is, thanks to the anti fat campaign and the resulting ubiquitous presence of sugar in practically every processed food and beverage, people are eating way more starchy, sugary, carbohydrates than in the past or in cultures that do eat starches but don't have a high rate of obesity and T2Diabetes. No one is saying all carbohydrates are a problem--fruits (in moderation), vegetables, nuts and seeds are fine--but over consumption of easily digested carbohydrates and constantly inundating the blood with glucose is going to eventually cause problems--how can it not? It may or may not cause fat gain, but it almost certainly will lead to T2diabetes, a much more serious consequence. Yes, obesity is a phenotype, but what is different between that phenotype and one that does not gain weight under the same circumstances? Again, Gary Taubes has a very plausible explanation in both "Good Calories, Bad Calories" and "Why We Get Fat."

I have read GCBC, and in fact Gary Taubes asked me for my comments on the manuscript of WWGF before it was published, which I was happy to do. I disagree with Gary on his carb = insulin spikes = fat gain hypothesis, and I do not agree that it is supported by "a mountain of both epidemiological and biochemical evidence". If you look at the evidence closely, it falls completely apart. Many of the animal models of obesity he discusses are models of leptin deficiency, but he then goes on to point the finger at insulin.

Hi gunther,

I'm not sure what you mean by calories in, calories out. Sorry to be picky, but people use that phrase in different ways. Calories in and calories out are both regulated by the brain, if that's what you mean.

This long post will is sure to please no one but if you have an opinion I would like to hear. The post is in 3 parts: the first is probably noncontentious, the second part is mild opinion with which most will agree to some extent. The last part is pure opinion and is my attempt to influence the general tone of discussion. What say?Humans evolved over thousands of generations to eat whatever was available not continuously but at intervals determined by hunting/gathering success. As the intervals between meals were likely of the order of a day, a metabolic system evolved for storing consumed calories as body fat and retrieving the calories as needed in the form of fatty acids, ie a caloric equilibrium so body fat is kept more or less constant. Such a system appears to be stable, not overly sensitive ie robust against temporary disturbances , and capable working well for long time as is observed in some people (today) and in some populations. If the process is disturbed sufficiently, equilibrium is lost (as happens in inanimate systems) and the process no longer works as before ie does not return to an equilibrium state. In humans such a disturbance is termed a pathology, eg obesity. A return to equilibrium may or may not be possible. Success (if possible) to re-establish equilibrium depends on many, mostly unknown complex factors (some of which may be dependent variables) as living organisms adapt to their condition as best they can. It appears that an increasing number of people today suffer from a metabolic disequilibrium. Despite consensus dietary advice the problem seem intractable.

Pure opinion (but seems plausible to me):Systems out of equilibrium will respond in their specific ways to attempted corrections. There are many ways to be out of equilibrium, each state will likely require a different approach. The number of states is unknown but likely vast.(Professional) Medical science has failed so far to provide biologically plausible explanations. This is not surprising as the subject is endlessly complicated and difficult. The certainty expressed is undeserved as evidenced by actual health outcome statistics. Population studies may be too broad to be practically useful on an individual basis .Armchair science by amateurs is educational if approached critically and can be very entertaining. Good investment in time if you plan to proceed to the next step ie experiment. Anecdotal reports suggest that there may be ways to re-establish good health via nutrition changes, but some of these approaches are contradictory and some are in strong conflict with conventional recommendations and so appear dangerous.

Pointed opinion:If the above logic holds then the approach most likely to succeed is systematic nutrition experimentation. To proceed one needs to be reasonably certain that harm will not follow in the short term and that requires an investment in acquiring knowledge how to proceed and how to gage progress. It is this specific knowledge/experience that is useful. Reliable reports of personal experience coupled with some conceptual education by experts (pro or amateur) can be of real help.

What is not useful (but may be interesting)Conventional dietary recommendations are useless, except as an education in analyzing muddled thinking.Debates about macronutrient ratios are useful as possible starting points for experiment.Debates about detail mechanisms leading to excess fat accumulation are not useful in a practical sense and to be useful as education require a considerable investment in molecular biochemistry. Much of the debate reveals profound ignorance. So a diversion, perhaps entertainment, and a possible start to acquiring real knowledge. Debates about paleo practices, conditions and nutrition details are unknowable, irrelevant and mostly silly.

Oh Mr Gatherer, you are correct. Obesity is way more complex than "insulin", trust me I know. I have felt what it is like to have high normal leptin while in the context of a low carbohydrate diet. I know the fidgeting energy you get when you over eat, I know the fact that you are always warm and energetic even if you don't eat all day, I know I can eat a ton of calories and hardly store any as fat, I know I can eat junk food and not experience hypoglycemia or other signs of insulin surges as easily.And, of the body mass I do obtain on leptin, my fat layer thins to nothing meanwhile my muscles are well developed. It is ALL FAT LOSS.

Compare and contrast to these several weeks without leptin injections.

1) I have gained a few pounds, almost all of them fat.2) I eat way more calories because I am way more hungry (since gaining body fat this has gotten better - the fatter I get, the better I feel, which makes sense since increasing my body fat is increasing my leptin).3) When I do eat more calories, I do not get that fidgeting wired nervousness. I just store it as fat.4) I feel as if I am in a fog. I am no where near as sharp or clear minded. My mood is much more subdued. I feel like my dopamine levels plummeted, basically, and this is observed in leptin deficient people by genetics - people who are congenitally leptin deficient have a major personality switch when they start leptin; they go from placid and passive and child like to assertive and aggessive and adult-like. This is most likely a result of normal dopamine levels (whereas leptin deficiency automatically means low dopamine levels in the brain). 5) my glucose tolerance sucks way worse and I need to eat ketogenically. I had to completely change how I was eating. Most days I eat very low carb again and this is the only way I can feel normal.6) Pretty sure my estrogen levels decreased a lot. My face is more gaunt and my hair fell out a bit.7) If I go many hours without eating, I get cold and lethargic. This never happened on leptin.

The thing about "insulin" is that many many things ultimately control insulin. Taubes et al make the mistake of assumign ONLY CARBS control insulin. Carbs are a huge factor but they are by no means the most important or exclusive one. Low leptin, for example, means high insulin. Leptin is actually used for insulinomas because it directly INHIBITS insulin release from insulin-producing cells. Low dopamine sensitivity also means high insulin. LOTS of things result in high insulin.

IT's sort of like saying "everyone in debt drinks too much starbucks" simply because of an observation that frequenting starbucks restaurants tends to be a factor in some people's debt. What is missing is that while it is true debt ultimately controls financial status, "drinking at starbucks" is not the exclusive factor nor is it always even a causative factor.

So it is with insulin and carbs and obesity. ALL obesity is a result of excessive insulin action on the fat cell - it is IMPOSSIBLE to store fat without insulin, ALL fat storage is from a high insulin activity on the fat cell. However, eating carbs is just one factor. There are so many others and not all of them are amenable to dietary intervention. An insulinoma often causes severe obesity unless the person is starved (or their fat cells are genetically resistant to insulin). The treatment for insulinoma is not carbohydrate restriction - this will just kill them. THe treatment for insulinoma is removal of the insulin secreting tumor (or, more recently, leptin treatment which as stated suppresses insulin release from insulin generating cells - dopamine also does this).

@ThomasThe koolaid tastes like losing 180 pounds and maintaining it for 8 years and knowing exactly how to do this with out ANY EFFORT AT ALL other than perhaps consciously choosing to eat certain things and not other things, plus take a shot every day, and a few supplements. 280 ->a hair over 110 at 5'5 doing this.Minus the shot, I am still thin, but it's no longer effortless, and the conscious control is now invested in under eating calories and moving more to suppress my natural body fat level (which is artificially high due to prior sensitization of my body fat tissue to insulin as a child and teenager - even though I am controlling the causative factors of obesity, I cannot cmpletely CORRECT my obesity without tricking my fat tissue into thinking it is fatter by injecting leptin... either that, or psychologically white knuckle it and force myself to restrict/force myself to move).

No I don't think every single case of obesity will respond - there are a LOT of kinds of obesity like there are a lot of kinds of causes of "coughing". Not all coughing responds to zpack, but a LOT do.

All fat people do have excesive insulin action - however not all will respond to carbohydrate restriction. It depends on the underlying pathophysiological reason for the high insulin action on the fat cell. For a lot of fat western people it is a direct result of fruit juice and sodas and coolattas and lattees and large portions of rice which we ignorantly eat thinking food is food and no food item is different than the other. Thats what I thought as a child. Food is food and I am naturally fat. If only someone had told me at 13 "hey, there's this thing called insulin and carbohydrate makes your body process a lot of it" I would never have been fat.

I naturally have a gynoid shape with large hips and butt (one of the few benefits of PCOS - high estrogen levels in puberty result in an exaggerated growth of fat cells in my hips and butt and a widening of my hips more than other women ...and unlike many others with PCOS, I was spared the beer belly). However due to skin removal surgeries my surgeon removed a disproportionate amount of fat cells from my butt & hips. This has resulting in my shape changing to a more balanced one - I store more fat in my arms, legs, and stomach now (not visceral fat, just fat in the skin on my stomach). I have to say this change is not particularly favorable. I miss my full butt, lol. I now have a flatter white girl looking butt. It's funny I always used to tell myself "well, self, I may have horrible skin and all these problems from my messed up endocrine system... BUT AT LEAST I HAVE A FULL ROUND BUTT IN SPITE OF BEING SKINNY so many people lose weight and get a horrible flat ass". Then I had surgery and woke up... poof FLAT BUTT SYNDROME. I was so paranoid and embarrassed for the longest time.

Since gaining a few pounds of fat over these months the flat butt syndrome has improved significantly but it's still way flatter.

The unfortunate thing I am seeing now as I am regaining weight is that my butt just isn't responding to the fat gain, due to the loss of fat cells... but my waist and my lower back is getting fatter.

That idiot surgeon. I didn't even ASK HIM to mess with my butt. I told him to liposuction my back. He did the frigging opposite, lol.

Now if I want to have the shape I used to have/ naturally had I need to get more surgery to correct the mistake he made (that is to say, I need to have fat cells removed from my back and abdomen and placed in my butt WHERE THEY USED TO BE until he sucked them out with a catheter while I was under general anesthesia and could not tell him "hey idiot, leave my butt alone, I like it thx".

But I've had so many reconstructive surgeries already due to my severe obesity. I've had a tummy tuck, butt lift, outer thigh lift, inner thigh lift, brachioplasty, breast reconstruction. All of this was necessary to give me some semblance of a normal appearance, and I have tons of stretch marks and scars in spite of it. And breast implants I never would have wanted or had if not for the fact it was necessary to reconstruct my breasts.I don't want any more surgery. IT already makes me down to think about everything I have needed and how much I Have spent of hard earned money.

So when people say "GEEE ITS THE WOO YOU TAKE THIS PERSONALLY" well duh, my life has been trashed, truly trashed in so many ways.

Is there a possibility that a "right for the wrong reason" element may be a contributor?

[speculation ahead]

Maybe insulin has been getting pointed at when it's merely an innocent bystander? Much in the way that trigs have been thought to be causative of cvd but instead seem to only indicate what a persons diet is comprised of. Or maybe it's involved differently than we have been indoctrinated to expect?

There are a few things that Woo has said that I have also found experientially accurate unfortunately I'm getting the impression you may be found dead with the word LEPTIN carved into your forehead so I'm a little doubtfull that it will be taken seriously.

I do absolutely agree that the traditional high carb bland hunter gatherer diet is health promoting and probably optimal for most of the planet. I think that carbs as a causative factor in obesity has been thoroughly debunked unless some bridge crossing element is introduced. You have definitely made a compelling case for that position.

Still, I have the sense that something's missing. That the broad stroke isn't quite covering all of the surface area.

I think the definition of "carb" may be important here. In Good Calories Bad Calories, Gary seemed to be talking about refined carbohydrates, not the types of carbs that might be consumed by a non-Westernized hunter-gatherer society.

Yesterday I had to walk through the grocery section of WalMart to find a cleaning product I needed. I was amazed. I passed stacks of sugared drinks, displays of chips and other snack food, shelves of breakfast cereal and freezer cases of ice cream. To find eggs or meat, I would have needed to go to the periphery of the store.

Americans are not eating plain microwaved potatoes and checking off the "starch" box on their list of macronutrients. They are eating refined carbs and they are eating lots of them. I realize that those who study obesity may not see this, but those of us who live in the real world see it. And those of us who are past middle age see about half of our friends with big guts and skinny legs, in the process of developing type 2 diabetes.

Refined carbs do not destroy your health in weeks, months or even years. Some people can eat them for a lifetime and not suffer ill effects. But for many people, decades of refined carb consumption is associated with the development of diabetes and high blood pressure. And switching to a low-carb diet seems to slow the progression of both conditions. Scientists may pooh-pooh the idea that excess insulin secretion in response to refined carbohydrates is related to obesity and the metabolic syndrome. For now, for me, it fits my observations and experience. I'll let it go at that.

Just an interesting observation; I have two cats, one cat got pretty sick about a month ago with an allergy, so the vet suggested an elimination diet, i.e. swapping from 'Whiskers' wet cat food in gravy/jelly/or dry cat food (consisting of wheat, meat etc), to gluten free, dry cat food (consisting of meat and rice grain). The one cat with the allergy needed to gain a bit of weight, and he did (but might be more to do with the medicine; regained appetite as his immune defenses kicked in). The other cat was quite muscly and was a bit over weight. The overweight cat, close to a month on this new cat food, has lost so much weight we have to take it to the vet, to see if he has worms. I have a sneaky suspicion it must be the change in cat food. The reason being when I put a bowl of the gluten free cat food down he wont eat the food. When I put the 'Whiskers' wet cat food in gravy down, he eats like he hasn't eaten for a good while. And he is literally skin and bone at this rate. It might have some relation to palatability.

It tells your liver to make less glucagon (result: less sugar leaving your liver, leading to less insulin and less protein breakdown; better fat oxidation).

http://www.pnas.org/content/107/11/4813.full.pdf+html

My first hand experience is that calorie restriction can not accomplish what leptin normalization can. IT is IMPOSSIBLE to just "Not eat" calories and obtain the amazing metabolic normality of a low dose leptin replacement. Even assuming you ignore the central effects of leptin (the ones telling you to EAT EAT EAT EAT)... you still have frequent hypos, you STILL can't eat carbohydrates normally without your hormones storing it as fat, you STILL waste protein tissue even if you eat a lot of protein it is all broken down into glucose, etc.

The effects of leptin are certainly central, but a lot of it is peripheral. It literally changes your entire metabolism and endocrine system so that you are naturally thin, assuming the diet is controlling glucose and insulin surges (crappy carbs or excessive carbs are not being consumed).

There are many types of diets that can reduce insulin, thus lead to fat being lost from the fat cell. However, obesity is a permanent condition in many people particularly those who gained weight rapidly as adolescents. You can reduce insulin & lose fat from your fat cell in many ways; but ANY AND EVERY way will result in relative as well as absolute hypoleptinemia.

This relative / absolute hypoleptinemia leads to a starvation syndrome which forces the person to either consciously "starve" every day to maintain weight, with physical as well as emotional sequellae... or alternatively, it forces you to eat more move less and replenish your fat cells until your leptin level reaches a sufficient point to terminate the starvation syndrome.

This is not "leptin resistance".

This is a normal and natural function of leptin under insulin's action. Insulin sensitizes your fat cells as a youth to grow, and excessive fat cells require excessive fat content to function properly; without this fat content, they will fail to produce leptin. Obese people who have lost weight produce very little leptin compared to matched controls who never lost weight. This is insulin sensitizing your fa

I will be zonky minded 10 mins after eating - the glucose rising in my brain leads to a buzzing in my head and an autistic-like hyperfocusing on just one noise on the environment, I feel locked out of awareness.

After 30 minutes when my insulin starts to rise to correct the high glucose, I will feel "normal" and full. Yes, insulin is anorexiant... for like the first 30 frigging minutes before your blood fatty acids and glucose and other nutrients bottom out. Factoid: insulin doesn't just usher glucose and fat into fat cells it also does this to numerous minerals. This may also play a role in disease, for example, excessive iron storage is implicated in various diseases and insulin has a role in this.

After 1 hour or 1.5 hrs, thats when the drama happens. I feel a tremorring in my body and a nervousness. I feel shaky. I get very emotional. I get very hungry. If I test my blood sugar it is usually in the low 70s at this time, sometimes high 60s, but at times it may be in the 50s if I was also doing activity at the time. One time I slammed 40 grams of dextrose to test my hypoglycemia. I went from 140 to 45 in an hour.

So I eat more food to correct this problem - But the shaking, tremorring, tension and hunger does not go away.Eventually the hunger does subside, but the tension and irritability and feeling "beat up" lasts ALL DAY. The hunger will rapidly come back if I made the same mistake - if I ate a lot of carbs like an idiot, then I can expect a repeat performance.

I lived my whole life like this, having low sugar over and over, until I found low carb.

I can eat fatty lamb, cheese, lasagna, cheesecake, egg omlettes with bacon and diet low carb bread and ketchup with no sugar added, I can eat all the nuts I want - sweetened and salted - I can eat dark chocolate, I can eat tons of cream in my coffee.

I can eat a wide variety of tastes and textures.

I ONLY HAVE PROBLEMS if the carbohydate content increases.

I assure you I eat far less cheesecake (no sugar added) than I will soggy week old rice or pasta or potatoes. The cheesecake will make me feel great and blood sugar stable. The starches will ruin me even though they taste horrible.

Jenna -My experience with cats and commercial cat food is that some commercial cat foods are engineered and designed to mess with the cat's appetite. They contain flavor enhancing additives that the cat eats ravenously.There are certain foods I can give my cat to eat, and he looks as if he is on catnip. These are usually the dried foods.

The obesity is a seperate issue, and that is a result of the taste-stimulated cat eating too many carbohydrates in the food, which just like a human will cause insulin surges, an inability to use stored fat, compensatory eating (due to an inability to access fat tissue nutrients) and more insulin surges.

The cat does not eat the low allergen diet as well because most likely these foods do not contain the flavor enhancing components of the more commercial food. As a result your cat is taking in far less rice carbohydrates, which is bringing his insulin down and he is accessing his stored fat.

We need to separate appetite from fat accumulation; if you added the flavor enhancers to an all meat diet (the one your cat evolved to eat) he would not become obese. It is only when the flavor enhancer is added to the unnatural carbohydrate diet that your cat becomes obese, because you are tricking this animal into consuming excessive dietary glucose and its endocrine system can only cope by storing lots of fat/not being able to access that fat.

Reproductive aged women have 3 times the leptin of men. Leptin plays a role in protecting women from many diseases that strike men (cardivascular, metabolic, mental health issues - leptin protects against all).

Leptin is very important in female physiology for evolutionary reasons (female reproductivity is highly dependent on nutrition status for obvious reasons).

2) Fat cell SIZE. Two people can have 10kgs of white adipose a piece; but if that fat is distributed amongst 3 times the fat cells in person A as compared to person B, then person A will make only a fraction of the leptin as person B. Person A will be in a starvation syndrome because his or her body fat is atrophied.This is a major factor in hypoleptinemia as pertaining to fat loss and dieting.

3)Insulin stimulating fat cells

Insulin acting on the fat cell to take up glucose, to stop releasing fatty acids, and to star storing fat is a major factor in leptin level. Fasted people will have relatively low leptin when compared to the fed state. This is the major reason fat people have such high leptin - their insulin is quite high and stimulating their copious fat tissue, resulting in high insulin.

4)Neurohormones also affect leptin. Dopamine reduces leptin, as dopamine causes fat to leave the fat cell and promotes fat burning. Serotonin does the opposite and so raises leptin.

Kidney diseases and many other chronic diseases will result in high leptin levels as well but this is not relevant to obesity.

Thanks for your thoughts! Makes sense! And at the same time I can recognise that my cat titbit quite possibly has absolutely no relevance to Stephan's theory, or yours, because cats optimum diet is apparently carnivorous, and humans, well, there's a mix up it seems, a bit of confusion . . . . . and a multitude of expressions . . .

Surely in your experience with multiple surgeries and needing to find adequate/correct medications/interventions etc you have learned or at least been counseled that to get the results you want you have to learn to advocate for yourself and interact in a way so as to be taken seriously rather than be dismissed as irrational?

I don't have to live your life to know that Stephan is accurately interpretting the studies that have been conducted or that he has corrected the misrepresentation of those same studies by amatuers.

I also don't have to have lived your life to know that the vast majority of the world lives on carbs without suffering any of the metabolic ills that classical low carb doctrine assigns to carb consumption.

Finally, I don't have to have lived your life to recognise that in my life several of your observations have been my observations also.

I'd like to be taken seriously in asserting that these things do seem to be specific to low carb in my experience though I admit that I do not know why and I do not believe that the current literature has the right answer.

Bentlyj74 said the vast majority of the world lives on carbs without suffering any of the metabolic ills that classical low carb doctrine assigns to carb consumption

As I said above, the type of carbs makes quite a difference. If the world is living on root vegetables, they will probably do quite well. If the world is living on Coke, Doritos and Häagen-Dazs ice cream, the outlook may not be so rosy.

Woo, I haven't heard before of leptin shots. (I had to twist a doc's arm pretty hard to convince him there was a *test* for leptin that he could order.) How did you learn of the possibility? Does a doc prescribe it for you? Are there books or other information sources you can refer us to?

Thanks for your indefatigable efforts to enlighten us. I am always glad to get information based on personal experience even if it seems "far out" at first.

Woo you are doing a great thing here in this blog comment section. This is the difference between a researcher and real life clinical medicine. You obviously must have been in the Amgen trials based upon all you wrote here. I am in complete agreement with what you have posted here and we think about leptin in the same light. I really like SG theories and his blog but nothing in my clinical experience of treating obesity follows any of his theories on leptin or food reward. As a neurosurgeon I can guarantee you obesity is a disease and it is a disease of signaling in the brain. Dr. K

Explain the doubling of diabetes worldwide since 1980s . I have watched forty years of college freshmen who used to come in thin, now I see them coming in fat or thin with potbellies. I see people who spent years trim, but hit their fifties and start to put on a lot of weight, with no change in diet. There were no fat kids in my rural elementary school in the 1950s; that same school now has as many or more fat kids. I was thin most of my life, then five years of chronic stress, insomnia, overwork turned me into a carb craver, gaining weight at 6-8# a year until I cut out all refined sugars, sweeteners, most carbs, and increased protein and fat. You don't have to be brilliant to see we have a tidlal wave of fattening agents swamping us.

Gunther, from what I could gather reading around it appears as though dopamine signalling helps partition ingested calories away from storage in adipocytes to other areas of the body for burning instead, basically giving you the "lean, muscular, sexually healthy" phenotype that we all find so aesthetically pleasing.

Consequently leptin signalling is a major factor in dopamine signalling, as ItsTheWoo2 said, low leptin signalling = messed up dopamine.

In light of this its easy to why Liposuction will result in fat gain elsewhere, a sudden drop in "full fat cells" will probably produce a sudden drop in leptin signalling, trick your brain into thinking your starving and preferentially partition calories towards fat storage.

The fat cells elsewhere in your body in order to acommodate for the extra incoming calories to be stored will have to hyperplasia.

The number of fat cells you have essentially determines your "body fat setpoint" if we accept the assumption that fat is stored in roughly equal proportionality bewteen fat cells.

@ItsTheWooo2, I have also experienced the anorexigenic action of insulin for a short while after eating carbs like grains and sugar. And just as you described, when blood sugar falls about two hours later, the irresistible urge to go back to the cupboard and gorge again because of extreme hunger. Lather, rinse, repeat for years until the scale told me I was morbidly obese and I hated myself for it.

@ Todd Hargrove, do you really think the carbs in sucrose, HFCS and refined grains are the same as the carbs in zucchini and broccoli? I would submit that physiologically they are quite different.

@Nancan, your experiences of stress, carb craving, weight gain, and relief after turning to a low-carb regimen match mine. It's good to hear your observations about students as well. I see a younger population of kids, but they seem to be heavier than they used to be.

@Stargazey: How does GT's theory explain potatoes? His theories just don't hold up when you look at the insulin responses to various foods, and sugar especially ... his new villain ... as half the carb in those refined foods elicits no insulin response.

@All: I am not surprised that this occurs. Reduce fat mass by a means that does not require any change in habits, continue habits, gain the fat back to where your body is in energy balance once again for your fat mass. That it repartitions to visceral depots is also not surprising since the fat cells aren't where they used to be and these adipocytes are more active.

Stephan said: "All this postprandial insulin spikes = fat gain stuff is nonsense as far as I can tell. I still haven't seen a shred of convincing evidence to support it, and in fact, the evidence I've seen mostly supports the opposite hypothesis, that insulin spikes oppose fat gain. The idea that postprandial insulin causes fat gain is contradicted by the most basic empirical facts in both human and animal studies. As I said before, I don't know a single person who studies metabolism/endocrinology professionally who takes that idea seriously-- it is confined to the popular press and internet blogs/forums. "

Dr Kruse, I'm not sure that yours and Stephan's positions are mutually exclusive.

For one, as far as I understand, exogenous leptin only helps with weight loss maintenance, not actual weight loss. And of course, there are no long-term studies that show what side effects even very low-dose leptin has over time.

But even if it it's useful/benign, it might well be akin to the current situation with T2D; exogenous insulin helps manage the disease, but so too does following a low-carb diet.

I happen to disagree with Stephan that it's only about palatability and not about reward, but in the standard American diet, the two are pretty inextricably linked.

And I think it's an easy inference that the reason that most diet trials show short-term success is that the problematic foods in our diet -- Kurt Harris' neolithic agents of disease -- tend to be removed, whether the diet is low-fat or low-carb, paleo or vegan.

Aye, but there's the rub: people find that they cannot stay on any constrained diet for life. This is why I'm currently experimenting with intermittent NAD's ;). This is essentially similar to the cheat day concept in Tim Ferriss' 4HB Slow Carb Diet (tho I'm following the Perfect Health variant).

The periodic NAD refeeds let off a little pressure wrt food reward, and may give a boost to the leptin system (which is why the Leangains folks use this to get to single-digit body fat percentages).

So are you saying that refeeds with the NAD's are more useful than just using plain old whole food starch refeeds? i have beaten obesity and used multile tools to do it and one of those was carb cycling but doing it while keeping "paleo". i don't get the cravings for the NAD and although i do gorge on paleo stuff periodically(once a month maybe) when i get ravenously hungry, my hypothalamus must be doing its job correctly again because my body wants to fast for about 24 hours or longer afterwards. that's what this energy balance thing is all about anyways right? if i've been slightly underfeeding myself, my body will want more food and then if i overfeed myself during the process, a healthy hypothalamus and leptin receptors will adjust accordingly. that's how i see it anyways and unless i make concerted efforts to move my setpoint one way or the other, my bodyweight stays constant. this is the first time in my life i've ever had a stable setpoint.

First a caveat. I haven't read Gary Taubes' latest book, so I can only reference GCBC. And I can't tell you what's in Gary's head.

What's in my head, lately, is that pre-diabetic carbs are different from post-diabetic carbs. If you are pre-diabetic, you can eat lots more carbs. If you stick to the carbs that were available to our hunter-gatherer ancestors, you will probably remain metabolically healthy.

If you go the sucrose/HFCS/refined grains route, you have a higher risk of developing type 2 diabetes after several decades. This is only personal opinion, but I think it has something to do with insulin spikes.

Once diabetes starts to develop, all carbs become problematic. Because of that, even potatoes produce intolerable swings in blood sugar and can only be eaten in moderation if the diabetes is to be controlled.

So (and again, this is personal opinion), potatoes eaten before the development of diabetes are probably fine. Potatoes eaten after diabetes starts to develop are an invitation to both high and reactively low blood sugars.

Stargazey said, I think the definition of "carb" may be important here. In Good Calories Bad Calories, Gary seemed to be talking about refined carbohydrates, not the types of carbs that might be consumed by a non-Westernized hunter-gatherer society.

I don’t know how much true distinction between “carbs” Taubes’ theory really makes because he tends to frequently “adjust” his theory on the fly, but in the Jimmy Moore interview he said explicitly that even the carbs in green leafy vegetables could be too much for some people. This seems to be a necessary argument to support the conjecture that “carbs are evil”, though it is quite a stretch and shows what a stretch Taubes theory ultimately is.

In the Fathead interview he said that the carbs in nuts and cheese could be too much and that these carbs could the true cause of the tendency of nuts and cheese to stall weight loss.

If such disparate foods as soda pop, pasta, nuts, and cheese all are problematic, then maybe it is pretty misguided to focus on “carbs” as the essence of the problem, even if you add the qualifier of “certain types” of carbs. “Carbs” is a misguided focus. Instead it should be that certain types of “food” are problematic.

Diet Pills, I have to agree with you that Gary Taubes seems to decide some things on the fly. And he's just plain wrong about some things. I addressed a whole blogpost to some of the discrepancies I found in GCBC. So I'm not here to defend Mr. Taubes.

However, as I expressed above, I am coming to the belief that, for everybody, hunter-gatherer carbs and post-industrial carbs are physiologically different. In many people, long-term ingestion of large amounts of post-industrial carbs (sugar, HFCS, refined grains) appears to lead to metabolic syndrome.

Once the metabolic syndrome (and especially type 2 diabetes) begins to develop, then all carbs start to become problematic. In fact anything that stimulates release of insulin (including excess protein) starts to become problematic.

Dr. Richard Bernstein deals with this all the time in a practical way. If you have the time, reading his book Diabetes Solution will give you insight into how adjusting carb and protein intake can help control the symptoms of diabetes.

Stargazey, someone (maybe Dr. Harris) had the analogy that just because someone with a damaged gallbladder may have to watch their fat intake, it does not mean that fats were the reason for the damaged gallbladder to begin with. By the same token, just because diabetics may have to watch their carbs, it does not follow that carbs caused the diabetes to begin with.

Right now I am leaning toward just excess calories probably being the main culprit, but I could see excess fructose and industrial seed oils leading to fatty liver (especially due to choline deficiency as Masterjohn theorized) and that leading to metabolic syndrome and diabetes.

i think the perspective needs to change on "carbs" in general. i think people should start talking in terms of glucose and fructose when talking about carbs because they are metabolized in different ways. all things being equal, glucose i benign and beneficial to many body functions. fructose is the one that is a bit more tricky and i believe there's enough evidence to point it being a major factor in insulin and leptin resistance.

but since all things aren't equal, glucose can indeed become problematic if pathologic insulin resistance has progressed to the point of type 2 diabetes. at that point, going low carb is probably the way to go. if it hasn't progressed that far yet, i think people can improve their insulin sensitivity using different tools such as cyclical ketogenic diets, strength training, and maybe some magnesium supplementation. that's been my experience and what i've observed. ymmv.

"do you really think the carbs in sucrose, HFCS and refined grains are the same as the carbs in zucchini and broccoli?" I think the key variable is not the type of carb in a particular food but the make up of non carb nutrients and toxins in the food. So the difference between fruit and sugar or refined wheat and sweet potatoes in not the type of carb in the food but the other "non carb stuff" that is also present in the food.

People without phenylketoneuria also live quite well eating all the protein they want. However, people with this disease must LIMIT the phenylaline they consume, or else they trigger their disease syndrome.

Did you ever stop to think maybe obesity is a disease?

Maybe pre-industrial humans can tolerate carbohydrate because their mitochondria and brain and body have not been sensitized to abnormal glucose levels and abnormal insulin surges and abnormal hyperleptinemia, and trace amounts of zyprexa in the water, and light deprivation, and depletion of insulin-signalling factors such as chromium and inositol, and severe omega 3 deficiency, and xenoestrogens which encourage fat cells to grow (which then raises minimum set point), etc etc etc.

Maybe pre-indusrial humans genetically do not have the aggregation of metabolically "inferior/weak" predisposing genes, because they were at such a risk to survival?

There are a lot of hypothetical explanations, but either way, obesity is a disease and if you have it you may require dietary prescriptions which don't apply to non-obese people. And no, gaining 15 or 20 pounds after 35 at a cushy desk job is not the same as pathologically storing hundreds of pounds of fat by the tme you are 20 years old. It is NOT the same thing, any more than the blues is psychotic depression, any more than having an achy ankle is a broken leg.

The problem is media and society (which loves to hate fat people) want us to think that the 300 pound person actively growing fatter is the same as the 120 pound person who gained 15 pounds. Oh, they're the same, meaning the 300 pound person is just that much lazier than the now 135 pound person (who can drop the 15 pounds if he or she stops eating the copious amounts of junkfood he or she is eating).

THere are many diseases out there which require certain dietary prescriptions. Why would you assume that obesity is different? Because oprah (and others) convinced you that obesity is not a biological disease, but rather an emotional problem of over eating junk food for comfort? Note that oprah is fatter than ever.

Oh, and I would point out Stephen does his fair share of misrepresenting data to fit his ever changing opinions about what causes obesity. The "low dopamine sensitivity as evidence of food addiction/reward" comes to mind. You can read my responses and invitation to logical deduction if you want to see what I think of that.

"Oh, and I would point out Stephen does his fair share of misrepresenting data to fit his ever changing opinions about what causes obesity."

You have got some nerve for someone who never provides references for her statements and bases her philosophy mostly on her own n=1 experience. I put up with your poorly thought out, unreferenced multi-post rants because, as I said, I like to allow alternative perspectives. I try to be patient because I know you have emotional issues. But I'm not going to put up with your juvenile accusations on my own blog.

If you think you have good ideas and you want to help people, organize them coherently and provide references on your own blog. The comments section here is not for your multi-page personal manifestos. One of the things that annoys me the most is arrogance, and you have it in spades. Don't let your head get too big or I'll kick you out, got it?

I've held my tongue here because this is not my blog. But I've been amazed Stephan has let you rant on as much as you have, and yet you can't even be gracious enough to withhold your condemnation about he he'll "never help anyone".

A genetic propensity towards obesity seems to exist in a very small (2-3%) percentage of humans, and this sounds like you.

What Stephan, and others, are trying to explain is why that percentage actually manifesting obesity is now several fold that. I may not agree in full, but we're all after an explanation of such things so that we can spare future generations the harms that obesity visits upon most. And perhaps help some who struggle with the consequences to reverse the situation.

I am curious at how you perceive your theory as different than Seth's? Or is your theory essentially the same as his, except perhaps his theory speculates more at the metaphor level and yours speculates more at the brain wiring level?

If different, then what sort of experiments could be designed to tease out the differences?

@Malibu Thank you, and 100% agreement. Leptin very effective for managing diabetes. Diabetes is mostly a glucagon (liver) problem. This is why "EAT ALL THE PROTEIN YOU WANT KIDS" advice given to diabetics (and glucose intolerant people in general) is bad.

And yes, studying starvation is very informative if you want to learn about leptin. Obesity has nothing to do with leptin unless it is a very rare leptin mediated form of obesity.

Weight reduction and attempts to REDUCE/RESOLVE obesity, however, is very much leptin related.

@Dr K yes, I was in the Amgen trials. Thank you for your support. There is so much nonsense being spread EVERYWHERE you look I figure I would be a lone rain drop ranting on the interet hoping to make some kind of difference. I know it won't help anything, it's all about money and power and the people with the money and power don't see what we see otherwise they would be all over this. There are very very few researchers out there who get it - leptin is the way to keep weight OFF, keep people STAYING on their diet, and that's the hard part.

There are a few clinical trials right now for leptin in the context of weight maintenance / loss. Most people are still screaming 'BUT ITS LEPTIN RESISTANCE LEPTIN REDUCTION IS WHAT IS NEEDED".

I have been a long time reader. I have read every blog post you've written. I have not agreed with every last word. Reasonable people can disagree. Even with the current Food Reward series, I have several questions/concerns still before buying-in.

Having said that, your blog remains one of the top, if not the top blog of thoughtful information presented in a manner that is accessible to all - even in the face of recondite and abstruse topics, or subject areas where clearly the "facts" are open to interpretation. I think you have been pretty forthcoming where you are asserting something as an "incontrovertible fact" vs "educated opinion" vs "hypothesis pending data" vs "etc". I have always respected this, which is one of the reasons I continue to return.

At the expense of being arrogant myself, I think you "owe" it to your long time readers to end this grandstanding by certain individuals, which is arguably hijacking your blog. I am not in any way suggesting dissenting opinions should be suppressed - far from it. However, dissent is one thing, being a flaming a-hole is another.

My 2 cents - turn off the comments. People can take the discussion to Paleo Hacks or other sites. Yes this will penalize the mostly innocent due to the handful of guilty. But completely selfishly speaking, I would rather you spend your time working on the next blog post than fielding confrontational posts from antagonists that seemingly have no agenda other than to be intransigent and concurrently disrespectful.

Stephan, Don't turn off comments if you can, sure there's some noise to signal but the comments are the icing on the cake of your posts, you attract some really smart people here, even if I don't understand a lot of what some of them say (looking in your direction mighto'chondri-al ;))

Anyway, thanks for all you do and for free!

I second a previous commenter, how would we test this hypothesis? I'm struggling to think of a good design. Can you have 'reward' without 'tastiness'? I guess I'm just having trouble separating the two in my mind.

I, for one, hope you don't turn comments off. However, I agree that Woo should show a little civility... and should start her own blog and present her whole case in a more systemic fashion. I would read it.

Thanks for the message. I see your point, but I don't plan on turning off comments because it's useful to some people, including me. I think people should have the opportunity to present their own experiences, dissenting views, etc. It also fosters a sense of community and helps me feel like I'm reaching people instead of firing off into thin air.

That being said, I do spend too much time on comments. Sometimes the interactions are productive, sometimes they aren't. I have been pulling back some lately because I have more constraints on my time now. Also, it's a pain to spend a lot of time in front of a computer.

Anyway, that's all to say that I'm still thinking about what my relationship should be with the comments. I won't be turning them off anytime soon.

Good move Stephan. Over the last 2 years or so I came across your blog and various others that happen to cross link, and all of them have proven to be most enlightening. As a lay person with growing interest in personal health, I have found the comments sections in blogs like yours and Peter's (to name just 2) to be almost more informative than the article they link to (in that they end to expand and qualify what was originaly written).

Whilst I don't think that you and Peter are always approaching things from the same perspective, I appreciate that you two can work alongside each other despite your differing views - and that is really what science is, is it not? That we don't know everything, but that we are willing to consider and test futher - always prepared to amend a long held bias when the evidence clearly points elsewhere.

Reading blogs like yours has encouraged me to learn and research more for myself and created the understanding within me that we take the word of nobody unless they can back it up.

As for the shouters - well, we learn to filter them out don't we. We are either here to learn and understand more or we are here to grind an axe and I'm not a lumberjack!

Brilliant article and quote about any useful obesity treatment having to addressing the fat mass regulatory system. I linked your article to my blog and want your message heard.

I wish more people out there on the Internet and the general public would realize what is known to all genuine obesity researchers: That the very highest quality research science (conducted by some of the best obesity scientists on the planet) demonstrates that up to 90 % of the variability in people's weights are due to GENES ( with environmental factors accounting for the rest) Dr. Jeffrey Friedman and Dr. Stunkard have boith shown that the genetic/hereditary component of obesity is MASSIVE.

And about 10 % of the extremely morbidly obese people are that way due to a single defective gene as Dr. Friedman has shown. He believes there is strong reason to suspect that number is significantly greater.

The general public has a lot of basless belief systems about obesity. Or perhaps it is ignorance on the topic.

Too many people think scientists highly qualified to assess the relevant scientific data ( such as yourself and Dr. Sharma) can be easily replaced by a Google search. So untrue.

Too many Internet gurus selling products and scamming poeple who do not know any better.

This is only going to end in me being banned or deciding to leave, clearly I will choose the latter.

There are tons of people on the internet spreading their personal ideas about what does or does not cause obesity (including myself); I have no idea why I am fixated on this blog, but either way, it is pointless for me to keep reading it when I almost never agree with the author and clearly get all worked up enough to rant on like every posts.

So to make things painless for all of us, I'll just duck out and I PROMISE not to post another disagreement again.

Everyone can release their righteous indignation because the drama has CEASED.

In case anybody is interested, ItsTheWooo2 does have a blog on Blogspot. Just Google "itsthewooo" and it will be the top selection.

The blog is sort of a personal journal and doesn't give the detailed analyses that we have seen here in Stephan's comments section. I don't always agree with Wooo, but I do thank her for the insights she has given me on leptin.

Woo, you were not told to shut up/get out, you were asked to be more civil. If you do not post again, I at least will miss you.

I do wish you had responded to my request for information:

= = = = =Woo, I haven't heard before of leptin shots... How did you learn of the possibility? Does a doc prescribe it for you? Are there books or other information sources you can refer us to?= = = = =

How can one reconcile "up to 90 % of the variability in people's weights are due to GENES" with the observed obesity epidemic of the last few decades? Surely, the genes of Americans have not changed that much in two generations.

"It's about choosing the right foods more than deliberately restricting how much you eat". Wise remark Stephan. Adding to this idea, I would suggest this article, "The Low-Carb Low-Down", by Jen Allbritton - http://bit.ly/ojh1Dz

Just to add another n=1 datapoint to the idea about carbs and weightloss. I had several weight fluctuations of around 30-40 lbs in my late teens and early 20s that came about as a result of junk food bingeing/stress. Then I basically kept the weight off for several years after college eating mostly lacto ovo vegetarian (budget issues as a grad student limited the meat protein I got). The weight did creep up over time at around 5 lbs per year, though. Three years ago I started a low carb diet. I lost 15 lbs, then another five through starvation and stress mostly through my wedding. This took a YEAR. Though I kept up with low carb (in my opinion, far longer than I should have) for a year after that, my weight crept up to the same point again. Another year of basically that continued strategy, plus throwing in more carbs from time to time, has not resulted in any weight gain or loss. I will grant that getting off of wheat was good for my mental state three years ago (I'm not going back), but in my experience, carbohydrates about around 30% are not a problem for me. Interestingly, when I don't obsess about macronutrients, I generally fall at around 1/3 calories from each. I do not eat refined foods, cheese, or nuts.

I think a reading of Taubes is good for anyone, and especially for people who are seriously overweight. I don't think anyone here will argue that eliminating refined carbohydrate is a good thing. What I see as a problem in the paleo/low carb communities is that this is turning into a religious fervor by those who have "seen the light" and those with alternative ideas are branded as heretics for acknowledging reality. I myself used to be a serious believer that Taubes' ideas could solve everyone's problems. After three years of eating as much saturated fat as I want and limiting carbohydrate to under 50 grams a day, I can conclude that this has been an abject failure for me in terms of weight loss. There are other anecdotal reports of people going onto a high fat, low carb paleo diet and gaining weight at paleohacks.

Different people will respond differently. My personal gut feeling is that if you have a lot of weight to lose, low carb and paleo will go far. If you are anywhere from 5 to 30 or 40 lbs. overweight, your mileage may vary with this approach and the further down you may need to go on Stephan's list of "5" to achieve success. I'm hardly there yet myself -- I don't know what will work to any extent, though I have lost about 5 lbs. on the bland food/Seth Roberts oil protocol so far, which is the lowest weight I've been at in a year. However, I do know what does not work for me: low carb.

Over the past month, it has struck me how many paleo bloggers are focused on making food taste good. As someone said in a previous thread, there's a big avoidance of the fact that in the paleolithic, food probably didn't taste all that great, at least according to modern conceptions about what is tasty (fatty, salty, sugary, Maillard products, etc.).

@Monica - It seems that implicit in your comment is what I regard as the key: there is no one diet that is right for everyone. In fact, it may even be that the "best" diet for a person may depend on their precise metabolic status at a given point in time.

Let's take the case of someone who needs to lose an extreme amount of weight (e.g. 200 lbs.) Could it not be the case that for the first 100 lbs. or so a very-low-carb approach is best, yet as metabolic function and insulin resistance improve a more "mediterranean" style diet could become more appropriate? I think that this is the great tragedy of much of the nutrition research that is happening today -- there is this impliied assumption that there is the One True Diet for Everyone and we just need to find it. Certainly, that's the logic implicit in the Food Pyramid (or the plate, or whatever they're using nowadays.)

As a case in point, consider Gardner's ATOZ study. He mentions in his YouTube presentation (http://www.youtube.com/watch?v=eREuZEdMAVo) of the study (but not, so far as I could find, in the published study), that the Atkins diet dramatically outperformed the other diets among those who were most insulin resistant. This is especially telling given that it only moderately outperformed the other diets on average -- suggesting that for those not insulin resistant it may have underperformed the other diets. (I'd love to get my hands on the raw data!) I suspect that, were we to peal back the covers on other studies, we might find a similar pattern.

JBG - I suppose I will stay, with mental note to be more civil. However it is getting very tiring having people attack me and then being called out when I reciprocate in kind. I don't enjoy saying personal offensive things. I like to speak forcefully and sarcastically but I don't like to be mean. It would be nice if others could feel the same way. Calling an idea / line of thought stupid vs insulting the person saying it is very different, we should have figured that out by the time we left gradeschool.If someone is going to insult me, not the idea, don't be surprised when you get it right back.

With that said...

I had access to leptin as a subject in a major clinical trial for Amgen, as Dr K guessed. I horded the leftover supplies (although not all of them, and I kick myself for throwing away the vials I did - the researchers didn't care if I kept them in or threw them away, I threw away probably a years supply of leptin like a moron. But I digress.)

I have since run out of my "stash" and for the past several weeks it's been just me and my baseline metabolism/leptin synthesis. Thus my previous postings should be viewed in this light.

Leptin can only be purchased for clnical trials, it is not presently being prescribed by physicians for anything. A vial of 11.2mg leptin is over half a grand, I think the last price quote I saw was $512.

To understand how expensive that is, consider that at a low-normal female physiological dose (0.04mg/kg) a vial would last me less than a week. I could get about 6 shots from one vial at this dose. That works out to $85 per day, or more.

Until these researchers and drug companies pull their heads out of their butts, we won't see leptin being used for obesity any time soon. 99% of obesity researchers think leptin reduction is GOOD for obesity (fact: just because high leptin is a sign of hyperinsulinemia and obesity does not necessarily mean that reducing leptin in existing obese people is good or helpful at weight loss - a drop in leptin is merely a passive marker of successful metabolic control therefore correlates with successful fat loss. The low leptin ITSELF, however, impedes weight and diet maintenance).

I am very thankful for experimenting with leptin. I had a hypothesis (that all post-weight loss symptoms are attributed to leptin deficiency), and it turned out I was absolutely correct. Every single unfavorable symptom I had after weight loss was turned around by the low dose leptin replacement, merely to a level of normal female physiologic range.

I also feel that having been on leptin for years has helped my metabolism work more normally.

1) Leptin is integral in fat cell apotosis. Treating a post obese person with leptin helps their body "normalize" after obesity as it helps excessive fat cells to die, which then means basal leptin levels will be higher at an equal fat mass.

2) The immune system seems to "react" to the recombinant protein with an end result that your native leptin levels are slightly higher after exposure to recombinant leptin (this occurs circa month three for most people, and it did in myself which is plainly evident from my leptin measurements during the study).

3) For myself, with mental issues, depression, and hypothalamic amenorrhea I feel as if the years on leptin has "cured" all of these conditions. My depression got much much better over the years of leptin treatment, which makes sense as it has been shown in studies to be very important in protecting brain from stress response and mental health.I still seem to be having reproductive cycles even though I have not taken leptin in 2 months; perhaps higher baseline leptin due to immune system sensitization is the reason.

Either way it was very instructive experimenting with leptin. All that I have learned can scarcely be communicated - going from a leptin deficient state to a leptin replete one intuitively teaches you so much about what does or does not cause obesity, what obesity is made of, what appetite means, and it highlights the long termnature of weight control. You can eat a lot today, you can eat nothing tomorrow... this is nothing, this means NOTHING. Long term your body knows what it is doing and you can not so easily alter your weight.

@JBG - What that means is if the environment is constant, 90% of weight differences are due to genes.

If you take two individuals and put them in a diet with pizza, pepsi, slurpies, doughnuts ont he desk at work, late nights, sleep deprivation, etc...

The weight difference between these two individuals will be 90% genetic. Meaning to say, the person who slows to a halt, becomes depressive, tired, diabetic, gains 200 pounds, vs the person who maintains a lean state and totally resists metabolic decompensation... genetics explain 90% of this difference.

As a subject in this trial, it's possible you may be entitled to "compassionate use" of leptin. Contact the study investigators and see if they have any further plans for leptin or a follow-up trial to the one you were in. If so, you may be eligible for the "expanded access" option. Or your physician, or study investigator, can submit an application on your behalf. For the expanded access option the medication would be offered free of cost. Not too sure about the individual option. Good luck and keep posting. You are very informative.

Woo, thanks for your extended description of your experience with leptin. It is very helpful. I hope that Stipetic's suggestions may pay off for you.

About the genes thing, I find it not unreasonable to believe, as you've said, "...if the environment is constant, 90% of weight differences are due to genes".

But what Razwell said is, "...up to 90 % of the variability in people's weights are due to GENES (with environmental factors accounting for the rest)." For reason previously given, I have trouble with that.

You should not "have trouble with that." It IS what the very best quality science has shown.There is this PERVASIVE completely incorrect Internet MYTH that the genes could not have changed. That is completely incorrect.

Furthermore, the GENES CAN change in a SINGLE generation. See my blog for the explanation of how natural selection actually works. It operates most powerfully over the short term.

Science has SOUNDLY shown that obesity is extremely genetic and almost as heritable as HEIGHT. Possibly equal and at worst oinly a SMIDGEN under height

This is a FACT.

What we now know from TOP SCIENCE is suuficient to stop the stigmatization of obesity COMPLETELY.

About Me

I'm a writer and science consultant with a background in neuroscience and obesity research. I have a BS in biochemistry and a PhD in neurobiology. I'm the author of "The Hungry Brain: Outsmarting the Instincts That Make Us Overeat".

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This blog is a compilation of my opinions. It's not advice; it's information that you can take or leave as you please. I don't intend it to replace professional medical consultation or treatment. Your health is in your own hands.